Kurzfassung

Objective: We here explore whether observed treatment effects of a putative disease-modifying osteoarthritis drug (DMOAD) are greater when cartilage morphometry is performed with rather than without knowledge of magnetic resonance imaging (MRI) acquisition order (unblinded/blinded to time point). Methods: In the FORWARD (FGF-18 Osteoarthritis Randomized Controlled Trial with Administration of Repeated Doses) randomized controlled trial, 549 knee osteoarthritis patients were randomized 1:1:1:1:1 to three once-weekly intra-articular injections of placebo, 30 jag sprifermin every 6 or 12 months (M), or 100 jag every 6/12 M. After year 2, cartilage segmentation of BL through 24 M MRIs was performed, with blinding to acquisition order. After year 5, 24 and 60 M MRIs were analyzed together, with unknown relative order, but with segmented BL images as reference (24 M unblinded vs. BL), by the same operators. Total femorotibial joint cartilage thickness (TFTJ_ThC) change was obtained for 352 participants analyzed under both conditions. Results: Twenty-four-month data read unblinded to order revealed a -35 +/- 44 jam lower TFTJ_ThC than blinded analysis (all groups: lower/upper bounds -120/+51 jam; correlation r2 = 97%). With unblinded analysis, the placebo group lost -46 +/- 57 jam TFTJ_ThC over 24 M, whereas 100 jag/every 6 M lost -2.2 +/- 73 jam (difference =44 jam [95% CI: 22, 66]). With blinded analysis, placebo lost -11 +/- 53 jam, whereas 100 jag/every 6 M gained 30 +/- 62 jam (difference = 40 jam [95% CI: 21, 60]). 100 jag sprifermin injected every 6 M showed statistically significant (p < 0.001) treatment effects on TFTJ_ThC, with Cohen D = -0.66 for unblinded and D = -0.69 for blinded analysis. Conclusions: These results do not reveal that detection of proposed DMOAD treatment is enhanced with MRIs read unblinded to order; rather, the sensitivity is similar to blinded analysis. Choices on blinded vs. unblinded analysis may thus be based on other criteria. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).